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Effects of subminimum inhibitory concentrations of antibiotics on the Pasteurella multocida proteome: a systems approach.

Nanduri B, Lawrence ML, Peddinti DS, Burgess SC - Comp. Funct. Genomics (2008)

Bottom Line: We then overlaid the differential protein expression data onto the P. multocida protein interaction network to study the bacterial response.We identified proteins that could enhance antimicrobial activity.Overall compensatory response to antibiotics was characterized by altered expression of proteins involved in purine metabolism, stress response, and cell envelope permeability.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.

ABSTRACT
To identify key regulators of subminimum inhibitory concentration (sub-MIC) antibiotic response in the Pasteurella multocida proteome, we applied systems approaches. Using 2D-LC-ESI-MS(2), we achieved 53% proteome coverage. To study the differential protein expression in response to sub-MIC antibiotics in the context of protein interaction networks, we inferred P. multocida Pm70 protein interaction network from orthologous proteins. We then overlaid the differential protein expression data onto the P. multocida protein interaction network to study the bacterial response. We identified proteins that could enhance antimicrobial activity. Overall compensatory response to antibiotics was characterized by altered expression of proteins involved in purine metabolism, stress response, and cell envelope permeability.

No MeSH data available.


Related in: MedlinePlus

Overall trends in protein expression in GO Slims commonto sub-MICs. For each GO Slim, the percentage of proteinswhose expression was either up (black bars) or down regulated (gray bars)is compared to the total entities in that GO Slim are shown for amoxicillin (a),chlortetracycline (b), and enrofloxacin (c). GO Slim categories are as follows:1, external encapsulating structure; 2, DNA metabolism; 3, nucleobase, nucleoside,nucleotide, and nucleic acid metabolism; 4, protein metabolism; 5,transcription; 6, protein biosynthesis; 7, response to stress; 8, carbohydratemetabolism; 9, catabolism; 10, structure molecule activity; 11, peptidaseactivity; 12, amino acid derivative metabolism; 13, generation of precursormetabolites and energy.
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fig2: Overall trends in protein expression in GO Slims commonto sub-MICs. For each GO Slim, the percentage of proteinswhose expression was either up (black bars) or down regulated (gray bars)is compared to the total entities in that GO Slim are shown for amoxicillin (a),chlortetracycline (b), and enrofloxacin (c). GO Slim categories are as follows:1, external encapsulating structure; 2, DNA metabolism; 3, nucleobase, nucleoside,nucleotide, and nucleic acid metabolism; 4, protein metabolism; 5,transcription; 6, protein biosynthesis; 7, response to stress; 8, carbohydratemetabolism; 9, catabolism; 10, structure molecule activity; 11, peptidaseactivity; 12, amino acid derivative metabolism; 13, generation of precursormetabolites and energy.

Mentions: We examined the overall trends of antibiotic effects on the 16 GO groups thatwere identified by GO SlimViewer (Table 2). After excluding general GO terms like cytoplasm, metabolism and so forth, 13 GOgroups were evaluated. For each GO group, we calculated the percentage ofproteins whose expression either increased or decreased, compared to the total entitiesin that GO group, for each antibiotic treatment. The trend of AMX was anoverall increase in protein expression, which could indicate the induction ofan adaptive response (Figure 2). Conversely, CTC and ENR had an overallsuppressive effect on protein expression, potentially indicating that CTC and ENR detrimentally affect P. multocida fitness at doses below MIC. Alternatively, this could be a compensatoryresponse by slowing metabolism.


Effects of subminimum inhibitory concentrations of antibiotics on the Pasteurella multocida proteome: a systems approach.

Nanduri B, Lawrence ML, Peddinti DS, Burgess SC - Comp. Funct. Genomics (2008)

Overall trends in protein expression in GO Slims commonto sub-MICs. For each GO Slim, the percentage of proteinswhose expression was either up (black bars) or down regulated (gray bars)is compared to the total entities in that GO Slim are shown for amoxicillin (a),chlortetracycline (b), and enrofloxacin (c). GO Slim categories are as follows:1, external encapsulating structure; 2, DNA metabolism; 3, nucleobase, nucleoside,nucleotide, and nucleic acid metabolism; 4, protein metabolism; 5,transcription; 6, protein biosynthesis; 7, response to stress; 8, carbohydratemetabolism; 9, catabolism; 10, structure molecule activity; 11, peptidaseactivity; 12, amino acid derivative metabolism; 13, generation of precursormetabolites and energy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2367384&req=5

fig2: Overall trends in protein expression in GO Slims commonto sub-MICs. For each GO Slim, the percentage of proteinswhose expression was either up (black bars) or down regulated (gray bars)is compared to the total entities in that GO Slim are shown for amoxicillin (a),chlortetracycline (b), and enrofloxacin (c). GO Slim categories are as follows:1, external encapsulating structure; 2, DNA metabolism; 3, nucleobase, nucleoside,nucleotide, and nucleic acid metabolism; 4, protein metabolism; 5,transcription; 6, protein biosynthesis; 7, response to stress; 8, carbohydratemetabolism; 9, catabolism; 10, structure molecule activity; 11, peptidaseactivity; 12, amino acid derivative metabolism; 13, generation of precursormetabolites and energy.
Mentions: We examined the overall trends of antibiotic effects on the 16 GO groups thatwere identified by GO SlimViewer (Table 2). After excluding general GO terms like cytoplasm, metabolism and so forth, 13 GOgroups were evaluated. For each GO group, we calculated the percentage ofproteins whose expression either increased or decreased, compared to the total entitiesin that GO group, for each antibiotic treatment. The trend of AMX was anoverall increase in protein expression, which could indicate the induction ofan adaptive response (Figure 2). Conversely, CTC and ENR had an overallsuppressive effect on protein expression, potentially indicating that CTC and ENR detrimentally affect P. multocida fitness at doses below MIC. Alternatively, this could be a compensatoryresponse by slowing metabolism.

Bottom Line: We then overlaid the differential protein expression data onto the P. multocida protein interaction network to study the bacterial response.We identified proteins that could enhance antimicrobial activity.Overall compensatory response to antibiotics was characterized by altered expression of proteins involved in purine metabolism, stress response, and cell envelope permeability.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.

ABSTRACT
To identify key regulators of subminimum inhibitory concentration (sub-MIC) antibiotic response in the Pasteurella multocida proteome, we applied systems approaches. Using 2D-LC-ESI-MS(2), we achieved 53% proteome coverage. To study the differential protein expression in response to sub-MIC antibiotics in the context of protein interaction networks, we inferred P. multocida Pm70 protein interaction network from orthologous proteins. We then overlaid the differential protein expression data onto the P. multocida protein interaction network to study the bacterial response. We identified proteins that could enhance antimicrobial activity. Overall compensatory response to antibiotics was characterized by altered expression of proteins involved in purine metabolism, stress response, and cell envelope permeability.

No MeSH data available.


Related in: MedlinePlus